The research in this laboratory is concerned with central visual pathways in the brain. The long-term objective is to determine how specific visual functions are encoded and transmitted within these pathways. This objective will be greatly facilitated by the development and use of non-invasive functional neuroimaging techniques such as functional magnetic resonance imaging (fMRI). The proposed research concerns the coupling between neural activity, brain metabolism and hemodynamics, which is fundamental to functional neuroimaging. The project will utilize this laboratory's extensive experience with studies of the visual system, and innovative combinations of microelectrode sensors to determine the relationships between neuronal responses, activity-dependent changes in tissue oxygenation (i.e. oxygen responses) and blood flow. The following investigations will be conducted. (1) Relationships between neural activity, tissue oxygenation and blood flow. Laser Doppler flow and combined microelectrode sensors will be used to determine key relationships between neural activity, tissue oxygenation and blood flow within central visual pathways of an animal preparation. The spatial-temporal relationship between neural activity and activity-dependent oxygen responses will be characterized. The consistency of this coupling for different brain lamina, brain regions, and stages of the aging process will be investigated. (2) Enhancement of activity-dependent oxygen responses. Stimulus, respiratory, and pharmacological factors will be explored to enhance the specificity and signal-to-noise ratios of activity-dependent oxygen responses in an animal preparation. (3) Neural, metabolic, and vascular coupling: applications to BOLD fMRI. Parallel fMRI measurements will be made in human subjects and the results compared with those obtained from the animal preparation. The goal is to improve the spatial resolution and specificity of blood-oxygen-level-dependent (BOLD) fMRI. These investigations are based on the considerable background this laboratory has in functional organization of central visual pathways. By use of innovative experimental techniques, it will be possible to establish rigorous links between neural, metabolic, and vascular factors that underlie the interpretation of fMRI. The use of non-invasive imaging has revolutionized brain science and has become a critical tool in the clinical diagnosis of disease. The planned studies will utilize the visual system to provide insights that will apply broadly to other brain functions.